ArticleAmerican journal of physiology. Endocrinology and metabolism2019
Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium.
Article in American journal of physiology. Endocrinology and metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Cardiometabolic effects of breastfeeding on infants of diabetic mothers.World journal of diabetes · 2023Article
- The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells.Journal of animal science and biotechnology · 2022Article
- Identification and characterization of alternative splicing variants of buffalo LXRα expressed in mammary gland.Scientific reports · 2022Article
- Aberrant RET expression affects normal mammary gland post-lactation transition, enhancing cancer potential.Disease models & mechanisms · 2022Article
- Strategies to gain novel Alzheimer's disease diagnostics and therapeutics using modulators of ABCA transporters.Free neuropathology · 2021Article
- The bovine cumulus proteome is influenced by maturation condition and maturational competence of the oocyte.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Liver X receptors (LXRs) are ligand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRα and LXRβ, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRα is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRα as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.
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